PUBLICATION
Antitumor Activity of Ruditapes philippinarum Polysaccharides Through Mitochondrial Apoptosis in Cellular and Zebrafish Models
- Authors
- Liu, M., Wang, W., Wang, H., Zhao, S., Yin, D., Zhang, H., Zou, C., Zou, S., Yu, J., Wei, Y.
- ID
- ZDB-PUB-250828-7
- Date
- 2025
- Source
- Marine drugs 23: (Journal)
- Registered Authors
- Keywords
- Ruditapes philippinarum polysaccharides, anti-colorectal cancer activity, mitochondrial apoptosis, zebrafish
- MeSH Terms
-
- Animals
- Antineoplastic Agents*/isolation & purification
- Antineoplastic Agents*/pharmacology
- Apoptosis*/drug effects
- Bivalvia*/chemistry
- Cell Proliferation/drug effects
- Colorectal Neoplasms*/drug therapy
- Colorectal Neoplasms*/pathology
- HT29 Cells
- Humans
- Membrane Potential, Mitochondrial/drug effects
- Mitochondria*/drug effects
- Mitochondria*/metabolism
- Polysaccharides*/isolation & purification
- Polysaccharides*/pharmacology
- Reactive Oxygen Species/metabolism
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 40863621 Full text @ Mar. Drugs
Citation
Liu, M., Wang, W., Wang, H., Zhao, S., Yin, D., Zhang, H., Zou, C., Zou, S., Yu, J., Wei, Y. (2025) Antitumor Activity of Ruditapes philippinarum Polysaccharides Through Mitochondrial Apoptosis in Cellular and Zebrafish Models. Marine drugs. 23:.
Abstract
Colorectal cancer (CRC) remains a predominant cause of global cancer-related mortality, highlighting the pressing demand for innovative therapeutic strategies. Natural polysaccharides have emerged as promising candidates in cancer research due to their multifaceted anticancer mechanisms and tumor-suppressive potential across diverse malignancies. In this study, we enzymatically extracted a polysaccharide, named ERPP, from Ruditapes philippinarum and comprehensively evaluated its anti-colorectal cancer activity. We conducted in vitro assays, including CCK-8 proliferation, clonogenic survival, scratch wound healing, and Annexin V-FITC/PI apoptosis staining, and the results demonstrated that ERPP significantly inhibited HT-29 cell proliferation, suppressed colony formation, impaired migratory capacity, and induced apoptosis. JC-1 fluorescence assays provided further evidence of mitochondrial membrane potential (MMP) depolarization, as manifested by a substantial reduction in the red/green fluorescence ratio (from 10.87 to 0.35). These antitumor effects were further validated in vivo using a zebrafish HT-29 xenograft model. Furthermore, ERPP treatment significantly attenuated tumor angiogenesis and downregulated the expression of the vascular endothelial growth factor A (Vegfaa) gene in the zebrafish xenograft model. Mechanistic investigations revealed that ERPP primarily activated the mitochondrial apoptosis pathway. RT-qPCR analysis showed an upregulation of the pro-apoptotic gene Bax and a downregulation of the anti-apoptotic gene Bcl-2, leading to cytochrome c (CYCS) release and caspase-3 (CASP-3) activation. Additionally, ERPP exhibited potent antioxidant capacity, achieving an 80.2% hydroxyl radical scavenging rate at 4 mg/mL. ERPP also decreased reactive oxygen species (ROS) levels within the tumor cells, thereby augmenting anticancer efficacy through its antioxidant activity. Collectively, these findings provide mechanistic insights into the properties of ERPP, underscoring its potential as a functional food component or adjuvant therapy for colorectal cancer management.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping